Physiology of the skeletal neuromuscular junction

Question 1

What type of motor neurones innervate skeletal muscle?

Answer 1

Myelinated axons with cell bodies in the spinal cord or brain stem

Question 2

When will the myelinated axons become unmyelinated?

Answer 2

When they are close to the muscle

Question 3

What is the neurotransmitter at neuromuscular junctions?

Answer 3

ACh

Question 4

What type of cell surrounds every terminal bouton?

Answer 4

Shwann cels

Question 5

What type of receptor is present at the post-synpatic membrane?

Answer 5

Nicotinic receptors

Question 6

Where can vesicles of ACh be found in the pre-synaptic terminal?

Answer 6

In the active zone

Question 7

What is the process in a neuromuscular synapse?

Answer 7

Synthesis of ACh
Process of ACh into vesicles
Movement of vesicles to active zone
Release of ACh when an action potential travels through the membrane causing the opening of Ca2+ channels, this causes the release of ACh from the vesicels into the synaptic cleft
ACh acts on nicotinic receptors and then is subsequently broken down

Question 8

How is choline transported into the pre-synaptic terminal?

Answer 8

By a choline transporter that also transports Na+

Question 9

How is ACh synthesised?

Answer 9

From choline and acetly CoA by ChAT

Question 10

Where is acetly CoA derived from?

Answer 10

Mitochondria

Question 11

What is the action of calcium in the pre-synaptic terminal?

Answer 11

Causes vesicles docked at the active zone to fuse with the presynaptic membrane to allow ACh to dissue into the synaptic cleft
This allows ACh to activate post-synaptic nicotinic receptors in the endplate region

Question 12

What is the structure of nicotinic receptors?

Answer 12

5 subunits of glycoproteins (2x alpha, beta, gamma and delta)

Question 13

What occurs when the nicotinic gate opens?

Answer 13

Na+ enters the muscle cell and K+ leaves

Question 14

When will nicotinic receptors open?

Answer 14

When 2 molecules of ACh bind to it

Question 15

How is the end plate potential generated?

Answer 15

The driving force for sodium is greater than that for potassium and therefore the membrane will be depolarised (voltage gets more positive)
If this is large enough, this will trigger the opening of Na+ channels around the end plate causing an all or nothing action potential

Question 16

What will one action potential in the motor nerve trigger?

Answer 16

One action potential and a subsequent twitch

Question 17

What effect will the action potential have on the muscle cell?

Answer 17

Will enter T tubules and cause release of calcium from the lateral sacs of the SR
Calcium will bind to troponin-tropomyosin complex allowing for the power stroke

Question 18

How is the action of ACh terminated?

Answer 18

Via AChE enzyme present at the end plate membrane that will break down ACh to choline and acetate

Question 19

What are the symptoms of neuromyotonia?

Answer 19

Cramps
Stiffness
Myotonia
Muscle twitches

Question 20

What is the effect does neuromyotonia have on the neuromuscular junction?

Answer 20

Autoantibodies against voltage-activated K+ channels in the motor neurone disrupting function causing repetitive firing

Question 21

How is neuromyotonia treated?

Answer 21

Anti-convulsants - carbamazepine and phenytoin which block Na+ channels

Question 22

What are the symptoms of lambert-eason myasthenic synrome?

Answer 22

Muscle weakness in limbs

Associated with small cell carcinoma of the lung

Question 23

What is the effect does LEMS have on the neuromuscular junction?

Answer 23

Autoantibodies against Ca2+ channels in the motor neurone terminal resultin gin reduced calcium entry in response to depolarization and hence reduced ACh release

Question 24

How is LEMS treated?

Answer 24

Anticholinesterases and potassium channel blockers

Increase conc of ACh within the synaptic cleft

Question 25

What are the symptoms of myasthenia gravis?

Answer 25

Increasing muscle weakness during periods of activity

Often weakness of eye and eyelid

Question 26

What is the effect does myasthenia gravis have on the neuromuscular junction?

Answer 26

Autoantibodies against nicotinic ACh receptors in endplate resulting in reduced number of functional channels and hence amplitude of e.p.p.

Question 27

How is myasthenia gravis treated?

Answer 27

Anticholinesterases and immunosuppressant agents (azathioprine)

Question 28

What is the effect does botulinum toxin have on the neuromuscular junction?

Answer 28

Exotoxin toxin that acts at motor neurone termins to irreversibly inhibit ACh release
Enzymatically modifies proteints on docking vesicles in active zone